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Introduction

Under physiological conditions, hepatic stellate cells store 80 % of the total vitamin
A in the whole body as retinyl palmitate in lipid droplets in the cytoplasm, and regulate
both transport and storage of vitamin A [1-3].

It has been demonstrated that animal or human individuals exposed to drugs such as
methadone, prednisone and phenobarbital, antiepileptics [4], and xenobiotics like the environmental contaminants DDT, PCD and dioxins have dramatic
changes in their retinoid metabolism and function.

Recent data demonstrate that top predators among Svalbard mammals and birds like polar
bear, arctic fox and glaucous gull accumulate relatively large amounts of persistent
organic pollutants [5]. Since it has been reported that vitamin A accumulates at near toxic doses in some
arctic predators [6] and recent data suggest that PCB and DDT may reduce the threshold for vitamin A-toxicity
[7], an increasing accumulation of persistent organic pollutants might eventually precipitate
vitamin A-toxicity in these animals. To elucidate the possibility of vitamin A-related
toxicity in arctic predators, we have performed a systematic characterization of the
hepatic vitamin A-storage, which is the best index of the vitamin A-status, in mammals
of the Svalbard archipelago.

Methods

After getting permission to hunt the animals from the district governor of Svalbard,
11 arctic foxes and 14 bearded seals, were caught in the Svalbard archipelago near
Longyearbyen (78Ø N, 15Ø E) in the period from August 1996 to September 2001. Three
polar bears were shot in self-defense at Svalbard February and August 1998 in Ny Ølesund
and Hornsund. Distribution and content of vitamin A in livers and other organs were
analyzed by morphological methods such as transmission electron microscopy, fluorescence
microscopy for detection of autofluorescence of vitamin A and gold chloride staining
[8] and high-performance liquid chromatography.

Results and Discussion

The amounts of vitamin A stored in livers of arctic animal are shown in Table 1. The median values are presented due to the relatively large individual variations.
These values are much higher than all other arctic animals studied as well as their
genetically related continental top predators (data not shown). The values are also
high compared to normal human values and experimental animals like mouse and rat (200Ø600
nmol per gram) [9].

Table 1. Total retinol concentration in liver and kidney from rats and arctic animals.

The concentration of total retinol in kidney is normally less that 1% of the concentration
in liver. However, following an intake of excessive amounts of vitamin A or after
experimental treatment with xenobiotics like HCB, TCDD and PCB, the concentration
in kidneys may increase several-fold [10,11]. Kidney total retinol may therefore be used as a biomarker for vitamin A-related
toxicity or excess. When we measured the kidney concentration of total retinol in
the top arctic predators we observed that polar bear and bearded seal had kidney levels
below 1% of their liver value (Table 1). Arctic fox, however, had kidney levels of about 9% of the liver values (Table 1).

Strong autofluorescence and gold chloride staining were present in hepatic stellate
cells of polar bear, arctic fox, and bearded seal (data not shown). The distribution
of stored vitamin A in the arctic animals was essentially the same as that published
previously in normal rat and human liver [2,3]. In livers of arctic fox, polar bear, and beared seal, stellate cells stored one
or two large lipid droplets in their cytoplasm (data not shown). In the kidney of
arctic foxes and bearded seals, interstitial cells (renal stellate cells) stored vitamin
A-lipid droplets (data not shown).

Increased kidney concentrations of total retinol in arctic fox most likely are a sign
of pollutant-induced vitamin A-toxicity. It is interesting to note that the highest
accumulation of organic pollutants in arctic animals occur in the arctic fox [12]. Relative decrease of liver concentration of total retinol in arctic fox might be
due to the decreased capacity for storage of vitamin A in hepatic stellate cells.

Acknowledgements

The authors are grateful to JØrn Eldar Fortun, Anders Friberg, and Trond Østaas for
their excellent hunting. We also thank the University Courses at Svalbard for their
generous assistance by allowing us to use their laboratory facilities in Longyearbyen,
the Norwegian Polar Institute and the District Governor at Svalbard.

References

Blomhoff R: Vitamin A in Health and Disease.

New York, Marcel Dekker Inc 1994.

Wake K: Sternzellen in the liver, perisinusoidal cells with special reference to storage of
vitamin A.